Vaccines can be made more than 25% effective by adding left-handed chiral gold nanoparticles as adjuvants, according to the results of a study by an international research team in China, the United States and Brazil. in a publication Nature In this study, the researchers reported the results of tests on human immune cells with their nanoparticles and in combination with a vaccine against the influenza virus. “The key to understanding the contribution of these nanoparticles is the concept of chirality, which applies to an object or system that cannot be superimposed on its mirror image,” explained André Farias de Moura, professor in the Department of Chemistry. at the Federal University of So Carlos (UFSCar).
The new technology and knowledge can now be exploited by vaccine developers, the team said. “It can be used by any manufacturer of any type of vaccine, including vaccines against SARS-CoV-2 or newer variants of influenza,” Moura said. We are not vaccine developers, but we are offering this basic knowledge as a novel technological platform for those who are.
The paper, published by Moura and colleagues, is titled “Enantiomer-dependent immunological response to chiral nanoparticles”, in which they conclude, “Here we show that achiral and left- and right-handed gold biomimetic nanoparticles can be used in vitro and in vivo.” The left-handed nanoparticles show significantly higher (1,258-fold) efficiency than their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, leading to nanoscale applications in immunology. The way to use chirality opens up.
Maura’s group in Brazil collaborated in the study with researchers affiliated with the University of Michigan in the United States and Jiangnan University in China. Moura is also a researcher with the Center for Development of Functional Materials (CDMF), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP.
Chirality is a type of heterogeneity. The word is derived from the ancient Greek word kheer for hand. The best example of abstinence is, perhaps, the difference between a left hand and a right hand. When we put our hands in front of the mirror, the hand we see on the right is our left hand and vice versa.
“Everything alive on Earth is chiral,” said Maura. “Chiral molecules can have completely different properties depending on whether they are left- or right-handed. Two chiral forms of the same molecule are known as enantiomers. A sad example is thalidomide, which The drug was prescribed for morning sickness to pregnant women in the late 1950s and 1960s. It caused babies to be born with a variety of malformations. One of the enantiomers in the substance had the expected therapeutic effect, but the other affected fetal organs. influenced.
Moura commented, and the team’s reported study, suggests that research in nanomaterials has advanced enough to enable scientists to completely isolate an enantiomer. Nature exploited this potential. “We started with gold nanoparticles, which are symmetric and lack chirality. They are achiral. We first induced chirality in them by interacting with the amino acid cysteine, and then forming them as light-harvesting antennae. accelerated the induced chirality by exposing it to polarized light using the amino acid phenylalanine,” he further explained.
Salinity is measured in a “G-factor” on a scale from minus two (-2) to plus two (+2). The process used in the study enabled the scientists to exceed 0.4 and resulted in three nanoparticles: the basic achiral gold nanoparticle, the right-handed enantiomer, and the left-handed enantiomer.
Moura said, “Initially we tested the nanoparticles on cultured human immune cells in vitro and found that chiral nanoparticles induced the production of substances associated with the immune response even in the absence of antigens—something capable of triggering antibody production.” substance too.” “This kind of reaction is exactly what a vaccine helps.”
The team further wrote, “We find that the nanoparticles bind to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)—namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like— Module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, production of immune signaling complexes known as inflammasomes, and maturation of mouse bone-marrow-derived dendritic cells.
Testing the L-P+ and Dp- nanoparticles with influenza virus vaccines in live mice, the team confirmed far greater efficacy with the left-handed nanoparticles. “We found that the enantiomers significantly enhanced the efficacy of the vaccine. Specifically, the left-handed enantiomer showed a 25.8% increase in efficacy compared to the right-handed enantiomer, and an even greater increase than the achiral nanoparticle, ” said Maura.
The authors further explained, “We injected C57BL/6 mice with a H9N2 influenza vaccine mixed with various nanoparticles. In agreement with our in vitro and in vivo data … the left-handed nanoparticles exhibited a better response than their right-handed counterparts.” increased influenza-specific antibody titer in: after injection of L-P+ nanoparticles, the response was 1,258-fold higher than in DP- nanoparticles, and lasted 91 days.
They further conclude, “These findings demonstrate the need for parametrization of nanoparticle chirality in biomedical and toxicological studies… The described chiral effects also raise the possibility of generating immune responses using precisely engineered chiral inorganic nanostructures, Thereby leading to a better understanding of their role in biological systems.”